Geranylgeranylation

Geranylgeranylation is a type of protein prenylation, a post-translational modification of proteins. It involves the addition of a 20-carbon geranylgeranyl group to the C-terminus of a protein, typically to a cysteine residue. This process is crucial for the proper functioning of the protein and its localization within the cell.

Process

Geranylgeranylation is catalyzed by geranylgeranyl transferase enzymes. There are two types of these enzymes: type I and type II. Type I enzymes add a geranylgeranyl group to the cysteine residue of a protein with a specific four-amino-acid sequence at the C-terminus, known as a CAAX motif. Type II enzymes add a geranylgeranyl group to the cysteine residue of a protein with a different C-terminal sequence.

The process of geranylgeranylation begins with the synthesis of geranylgeranyl pyrophosphate (GGPP), a 20-carbon molecule derived from isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP). This synthesis is catalyzed by the enzyme geranylgeranyl diphosphate synthase.

The GGPP molecule is then attached to the target protein by the geranylgeranyl transferase enzyme. This attachment occurs through a thioether bond between the sulfur atom of the cysteine residue and the terminal carbon atom of the GGPP molecule.

Function

Geranylgeranylation plays a crucial role in the localization and function of several proteins. It is particularly important for the function of small GTPases, such as those in the Ras superfamily. These proteins are involved in a variety of cellular processes, including cell growth, differentiation, and apoptosis.

In addition to GTPases, several other proteins are known to undergo geranylgeranylation. These include nuclear lamins, which are important for maintaining the structure of the nuclear envelope, and peripheral membrane proteins, which are associated with the plasma membrane.

Clinical significance

Abnormalities in geranylgeranylation have been linked to a variety of diseases, including cancer, cardiovascular disease, and progeria, a premature aging syndrome. Inhibitors of geranylgeranylation, such as statins and bisphosphonates, are currently used in the treatment of these diseases.

File:Geranylgeranylation.png

Geranylgeranylation of a protein. The geranylgeranyl group (in red) is attached to the cysteine residue of the protein (in blue).

See also

• Prenylation
• Farnesylation
• Protein targeting
• Post-translational modification